Cationic contact lenses

Abstract

Disclosed is a cationic contact lens and a method for manufacturing the same. The cationic contact lens includes a polymeric lens body, which is a reaction product of a polymerizable composition that includes at least one siloxane, at least one nonionic hydrophilic monomer, and at least one non-cyclic tertiary amine monomer. The cationic contact lens can be a sterile silicone hydrogel contact lens that has not been worn. The contact lens is capable of substantially linearly releasing a releasable anionic agent and the at least one non-cyclic tertiary amine monomer facilitates uptake and / or sustained release of the releasable anionic agent by the polymeric lens body. The contact lens can be present in a sealed contact lens package. The sealed contact lens package can at least include a) a base member having a cavity; b) a contact lens encapsulation solution in the cavity; c) a sterile, unworn contact lens immersed in the contact lens encapsulation solution in the cavity, wherein the releasable anionic agent is present; and d) a cover that forms a liquid-tight seal with the base member.

Description

FIELD OF THE INVENTION

[0001] The field of the present invention relates to contact lenses and sealed contact lens packages, and more particularly to contact lenses having cationic properties, and further to packages containing such contact lenses, and methods of making such contact lenses. The contact lenses of the present invention having cationic properties may be regarded as cationic contact lenses. The contact lenses provide the ability to controllably release one or more comfort agents or other beneficial agents in the form of releasable anionic agents. BACKGROUND OF THE INVENTION

[0002] One of the main ways to improve contact lens comfort is to introduce one or more comfort agents into the lens material or the packaging solution. When the lens is placed on the eye, the comfort agent is released onto the eye surface. However, achieving controlled release of the comfort agent during contact lens wear has always been a challenge because the comfort agent is trapped inside the lens material, releases limitedly, or exhibits burst release rather than the desired controlled release, or does not provide release for a continuously desired period of time, which may be 8 hours or longer.

[0003] Accordingly, there is a need in the industry for contact lenses that can provide controlled release of comfort agents or an improvement in the controlled release of comfort agents. In addition, there will also be a need to provide such controlled release characteristics without significantly affecting other characteristics provided by the contact lenses. SUMMARY OF THE INVENTION

[0004] The present invention features a contact lens that can release a comfort agent during lens wear and avoid burst release of the comfort agent.

[0005] An additional feature of the present invention is to provide a sterile, unworn contact lens that is a silicone hydrogel and has cationic properties.

[0006] Another feature of the present invention is to provide a silicone hydrogel contact lens that includes a comfort agent that can be released and has a controlled release over a continuously extended period of time when worn in the eye.

[0007] An additional feature of the present invention is to provide a silicone hydrogel contact lens that has a higher ability to uptake and release comfort agents than conventional silicone hydrogel contact lenses.

[0008] An additional feature of the present invention is to provide a contact lens that can be loaded or reloaded with a comfort agent by contacting the contact lens with an eye drop containing the comfort agent or a multi-purpose contact lens care solution.

[0009] Additional features and advantages of the present invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the present invention. The objectives and other advantages of the present invention will be realized and attained by means of the elements and combinations particularly pointed out in the description and appended claims.

[0010] To achieve these and other advantages and in accordance with the purpose of the present invention, as embodied and broadly described herein, the present invention in part relates to a silicone hydrogel contact lens having (i) a polymeric lens body which is a reaction product of a polymerizable composition comprising from 15 wt.% to 65 wt.% of at least one siloxane monomer, from 25 wt.% to 75 wt.% of at least one nonionic hydrophilic monomer, and from 0.1 wt.% to 15 wt.% of at least one non-cyclic tertiary amine monomer, and (ii) at least one releasable anionic agent. The at least one non-cyclic tertiary amine monomer advantageously facilitates the uptake and / or sustained release of the at least one releasable anionic agent by the polymeric lens body. It has been found that both 2-(dimethylamino)ethyl methacrylate (DMAEMA) and 3-(dimethylamino)propyl methacrylate (DMAPMA) are particularly suitable non-cyclic tertiary amine monomers.

[0011] The present invention further relates to a silicone hydrogel contact lens comprising a polymeric lens body which is a reaction product of a polymerizable composition comprising: from 25 wt.% to 55 wt.% of a siloxane monomer; from 30 wt.% to 55 wt.% of a vinyl monomer selected from N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or combinations thereof; from 0.1 wt.% to 10 wt.% of 2-(dimethylamino)ethyl methacrylate; and optionally from about 1 wt.% to about 20 wt.% of a hydrophilic monomer selected from: N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), or ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof; and optionally from about 1 wt.% to about 20 wt.% of a hydrophobic monomer selected from: methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof.

[0012] The present invention further relates to a silicone hydrogel contact lens comprising a polymeric lens body, which is a reaction product of a polymerizable composition comprising: 25 wt.% to 55 wt.% of a siloxane monomer; 30 wt.% to 55 wt.% of a vinyl monomer selected from N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or a combination thereof; 0.5 wt.% to 3 wt.% of 3-(dimethylamino)propyl methacrylate; and optionally about 1 wt.% to about 20 wt.% of a hydrophilic monomer selected from: N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), or ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof; and optionally about 1 wt.% to about 20 wt.% of a hydrophobic monomer selected from: methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof. Contact lenses that are reaction products of such compositions have been found to have particularly good dimensional stability.

[0013] Additionally, the present invention relates to an unworn, sterile silicone hydrogel contact lens comprising a polymeric lens body, which is a reaction product of a polymerizable composition comprising 15 wt.% to 65 wt.% of at least one siloxane monomer, 25 wt.% to 75 wt.% of at least one nonionic hydrophilic monomer, and 0.1 wt.% to 15 wt.% of at least one acyclic tertiary amine monomer. The unworn, sterile silicone hydrogel contact lens is advantageously capable of substantially linearly releasing a releasable anionic agent at a release rate of at least 6 μg / hour for at least 8 hours. The at least one acyclic tertiary amine monomer advantageously facilitates the uptake and / or sustained release of the releasable anionic agent by the polymeric lens body.

[0014] Furthermore, the present invention relates to a method of manufacturing the silicone hydrogel contact lens of the present invention. The method comprises the steps of: a) polymerizing a polymerizable composition (as described herein) in a contact lens mold to obtain a polymeric lens body, b) removing the polymeric lens body from the contact lens mold, c) extracting the polymeric lens body in an organic solvent, d) hydrating the polymeric lens body in a hydrating liquid to obtain a silicone hydrogel contact lens, e) sealing the hydrated silicone hydrogel contact lens in a package with a packaging solution, and f) autoclaving the package, wherein at least one of the organic solvent, the hydrating liquid, or the packaging solution contains at least one releasable anionic agent.

[0015] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are intended to provide further explanation of the claimed invention.

[0016] The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate certain features of the invention and, together with the description, serve to explain the principles of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1A Graph showing the amount of anionic agent released from a cationic silicone hydrogel contact lens compared to a control lens.

[0018] Figure 1B Graph showing the percentage of anionic agent released from a cationic silicone hydrogel contact lens compared to a control lens. DETAILED DESCRIPTION

[0019] Contact lenses having cationic properties and methods of making the same are described herein. One or more contact lenses having one or more cationic properties may be referred to herein as cationic contact lenses. A sealed contact lens package including a contact lens is also described herein.

[0020] In the present invention, the cationic contact lens preferably provides for the controlled release of one or more anionic agents (such as anionic comfort agents or other beneficial anionic agents) during contact lens wear, which may dissociate from the polymeric lens material under physiological conditions during wear.

[0021] With respect to the contact lenses of the present invention, the contact lenses are unworn, sterile hydrogel contact lenses. In other words, the contact lenses are unused and new.

[0022] The hydrogel contact lens is the reaction product of a polymerizable composition including a non-cyclic tertiary amine monomer.

[0023] As an example, the hydrogel contact lens is the reaction product of a polymerizable composition of a non-silicone hydrogel including at least one non-cyclic tertiary amine monomer. Non-silicone hydrogel contact lenses are typically formed by the polymerization of one or more hydrophilic monomers (such as 2-hydroxyethyl methacrylate (HEMA) or vinyl alcohol) optionally in combination with other monomers and do not contain siloxanes (i.e., molecules containing at least one Si—O group).

[0024] As an example, the silicone hydrogel contact lens is the reaction product of a polymerizable composition including at least one siloxane monomer, at least one nonionic hydrophilic monomer, and at least one non-cyclic tertiary amine monomer.

[0025] As another example, the silicone hydrogel contact lens is the reaction product of a polymerizable composition including at least one siloxane monomer, at least one nonionic hydrophilic monomer, at least one non-cyclic tertiary amine monomer, and at least one hydrophobic monomer.

[0026] Generally, a "monomer" can include or refer to a molecule containing a polymerizable carbon-carbon double bond (i.e., a polymerizable group) that is capable of reacting with the same or different other molecules containing polymerizable groups to form a polymer or copolymer. The term monomer encompasses polymerizable prepolymers and macromonomers, and there is no size limitation on the monomer unless otherwise specified. A monomer can contain a single polymerizable carbon-carbon double bond or more than one polymerizable group and thus has crosslinking functionality.

[0027] When referring to the reaction product of a polymerizable composition, at least one siloxane monomer can be one siloxane monomer or two or three or more siloxane monomers.

[0028] As used herein, the term "siloxane monomer" is a molecule containing at least one Si—O group and at least one polymerizable group. Siloxane monomers used in contact lens compositions are well known in the art (see, for example, U.S. Patent No. 8,658,747 and U.S. Patent No. 6,867,245). (All patents and publications mentioned herein and throughout are incorporated by reference in their entirety.)

[0029] In some instances, the polymerizable composition contains at least 10 wt.%, 15 wt.%, 20 wt.%, 25 wt.%, or 30 wt.% up to about 40 wt.%, 45 wt.%, 50 wt.%, 55 wt.%, 60 wt.%, or 65 wt.% of the total amount of siloxane monomers. For example, at least one siloxane monomer can be present in an amount of 15 wt.% to about 65 wt.% based on the weight of the polymerizable composition.

[0030] Generally, unless otherwise specified, as used herein, a given weight percentage (wt.%) of a component of a polymerizable composition is relative to the total weight of all polymerizable components (and any optional polymers or other components that may be present) in the polymerizable composition. The weight contributed by components such as diluents that are not incorporated into the final contact lens product is not included in the wt.% calculation.

[0031] Exemplary siloxane monomers are those used in the following FDA-approved silicone hydrogel materials: asmofilcon A, balafilcon A, comfilcon A, delefilcon A, enfilcon A, fanfilcon A, galyfilcon A, kalifilcon A, lotrafilcon A, lotrafilcon B, narafilcon A, narafilcon B, olifilcon A, riofilcon A, samfilcon A, senofilcon A, senofilcon B, senofilcon C, somofilcon A, and stenfilcon A.

[0032] The nonionic hydrophilic monomer(s) can be present in the reaction product of the polymerizable composition in an amount of at least 10 wt.%, 15 wt.%, 20 wt.%, 25 wt.%, or 30 wt.% up to about 40 wt.%, 45 wt.%, 50 wt.%, 55 wt.%, 60 wt.%, 65 wt.%, 70 wt.%, or 75 wt.%, by weight of the polymerizable composition. For example, at least one nonionic hydrophilic monomer can be present in an amount of 25 wt.% to about 70 wt.%, by weight of the polymerizable composition.

[0033] As used herein, with respect to nonionic hydrophilic monomers, at least one nonionic hydrophilic monomer is understood to include a single hydrophilic monomer or a hydrophilic monomer component composed of two or more (such as two, three, four, or more) hydrophilic monomers.

[0034] The hydrophilicity or hydrophobicity of a monomer can be determined using conventional techniques (e.g., based on the water solubility of the monomer). For the purposes of this disclosure, a hydrophilic monomer is a monomer that is appreciably soluble in an aqueous solution at room temperature (e.g., about 20 °C to 25 °C). For example, as determined by the standard shake flask method known to those of ordinary skill in the art, a hydrophilic monomer is understood to be any monomer for which 50 grams of the monomer is appreciably completely soluble in 1 liter of water at 20 °C (i.e., ≥ 5% soluble in water). As used herein, a hydrophobic monomer is a monomer that is appreciably insoluble in an aqueous solution at room temperature such that a separate visually distinguishable phase is present in the aqueous solution or such that the aqueous solution appears cloudy and separates into two distinct phases over time after standing at room temperature. For example, a hydrophobic monomer is understood to be any monomer for which 50 grams of the monomer is not appreciably completely soluble in 1 liter of water at 20 °C.

[0035] Non-silicon non-ionic hydrophilic monomers that can be used as hydrophilic monomers or hydrophilic monomer components in the polymerizable compositions disclosed herein include, for example, acrylamide-containing monomers, or acrylate-containing monomers, or acrylic acid-containing monomers, or methacrylate-containing monomers, or methacrylic acid-containing monomers, or vinyl-containing monomers, or any combination thereof. It should be understood that the hydrophilic monomers or hydrophilic monomer components are non-silicon monomers.

[0036] Examples of non-ionic hydrophilic monomers include, but are not limited to: N,N-dimethylacrylamide (DMA), or 2-hydroxyethyl acrylate, or 2-hydroxyethyl methacrylate (HEMA), or ethoxyethyl methacrylamide (EOEMA), or 2-hydroxypropyl methacrylate, or 2-hydroxybutyl methacrylate (HOB), or 2-hydroxybutyl acrylate, or 4-hydroxybutyl acrylate, glycerol methacrylate, or 2-hydroxyethyl methacrylamide, or polyethylene glycol monomethacrylate, or methacrylic acid, or acrylic acid, ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof.

[0037] The non-ionic hydrophilic monomer can be at least one hydrophilic vinyl monomer. As used herein, a "hydrophilic vinyl monomer" is any hydrophilic monomer that does not contain siloxane (i.e., does not contain Si-O groups) and has a polymerizable carbon-carbon double bond (i.e., a vinyl group) in a part of its molecular structure that is not an allyl group, wherein under free radical polymerization, the reactivity of the carbon-carbon double bond of the vinyl group is lower than that of the carbon-carbon double bond present in the polymerizable methacrylate group. As used herein, the term "allyl group" refers to a polymerizable group present in acrylate, methacrylate, acrylamide, etc. Thus, although a carbon-carbon double bond is present in the acrylate group and the methacrylate group as used herein, such polymerizable groups are not considered vinyl groups.

[0038] Examples of hydrophilic vinyl monomers that can be provided in the polymerizable composition include, but are not limited to: N-vinylformamide, or N-vinylacetamide, or N-vinyl-N-ethylacetamide, or N-vinylisopropylamide, or N-vinyl-N-methylacetamide (VMA), or N-vinylpyrrolidone (NVP), or N-vinylcaprolactam, or N-vinyl-N-ethylformamide, or N-vinylformamide, or N-2-hydroxyethyl vinyl carbamate, or N-carboxy-β-alanine N-vinyl ester, 1,4-butanediol vinyl ether (BVE), or ethylene glycol vinyl ether (EGVE), or diethylene glycol vinyl ether (DEGVE), or any combination thereof. In one example, the hydrophilic monomer or hydrophilic monomer component comprises VMA, NVP, or both VMA and NVP.

[0039] In one example, the polymerizable composition comprises from at least 10 wt.%, 15 wt.%, 20 wt.%, or 25 wt.% up to about 45 wt.%, 50 wt.%, 55 wt.%, 60 wt.%, 65 wt.% or 75 wt.% of a hydrophilic vinyl monomer. As used herein, the given weight percentage of a particular class of components (e.g., hydrophilic vinyl monomers, siloxane monomers, etc.) in the polymerizable composition is equal to the sum of the wt.% of each component belonging to said class in the composition. Thus, for example, a polymerizable composition comprising 5 wt.% BVE and 25 wt.% NVP and no other hydrophilic vinyl monomers is said to comprise 30 wt.% of hydrophilic vinyl monomers. In one example, the hydrophilic vinyl monomer is an N-vinylamide monomer. Exemplary hydrophilic N-vinylamide monomers are VMA and NVP. In a particular example, the polymerizable composition comprises at least 25 wt.% (e.g., 25 wt.% to 55 wt.%) of at least one vinylamide monomer. In another particular example, the polymerizable composition comprises from about 25 wt.% up to about 75 wt.% (e.g., 25 wt.% to 55 wt.%) of VMA or NVP or a combination thereof.

[0040] Based on the total weight of the polymerizable composition, the acyclic tertiary amine monomer may be present in the reaction product of the polymerizable composition in an amount of 0.1 wt.% to about 15 wt.%, such as 1 wt.% to 14 wt.%, 1 wt.% to 12 wt.%, 1 wt.% to 10 wt.%, 1 wt.% to 7 wt.%, 1 wt.% to 5 wt.%, 5 wt.% to 15 wt.%, 6 wt.% to 15 wt.%, 8 wt.% to 15 wt.%.

[0041] The acyclic tertiary amine monomer can be regarded as a cationic monomer.

[0042] As used herein, with respect to the acyclic tertiary amine monomer, at least one acyclic tertiary amine monomer can be understood to comprise a single acyclic tertiary amine monomer, or an acyclic tertiary amine monomer component comprising two or more (such as two, three or four or more) acyclic tertiary amine monomers.

[0043] An acyclic tertiary amine monomer is a monomer in which the nitrogen of the tertiary amine group is not part of a ring structure, although the monomer may contain a ring structure (e.g., N-(2-aminoethyl)aminomethylstyrene). The term "tertiary amine group" should be understood to refer to a nitrogen atom directly bonded to three carbon atoms, provided that none of said carbon atoms is part of a carbonyl group.

[0044] Exemplary acyclic tertiary amine monomers include, but are not limited to: 2-(dimethylamino)ethyl acrylate, or 2-(diethylamino)ethyl acrylate, or 3-(dimethylamino)propyl acrylate, or 3-(diethylamino)propyl acrylate, or 2-(dimethylamino)ethyl methacrylate, or 2-(diethylamino)ethyl methacrylate, or 3-(dimethylamino)propyl methacrylate, or 3-(diethylamino)propyl methacrylate, or N-(2-(dimethylamino)ethyl)acrylamide, or N-(2-(diethylamino)ethyl)acrylamide, or N-(3-(dimethylamino)propyl)acrylamide, or N-(3-(diethylamino)propyl)acrylamide, or N-(2-(dimethylamino)ethyl)methacrylamide, or N-(2-(diethylamino)ethyl)methacrylamide, or N-(3-(dimethylamino)propyl)methacrylamide, or N-(3-(diethylamino)propyl)methacrylamide, or 3-(diethylamino)propyl vinyl ether, or 3-(dimethylamino)propyl vinyl ether or any combination thereof.

[0045] A more specific example of the acyclic tertiary amine monomer is 2-(diethylamino)ethyl methacrylate, which may be present in the polymerizable composition in an amount of 0.1 wt.% to 15 wt.% or 1 wt.% to 10 wt.% (based on the total weight of the polymerizable composition).

[0046] Another specific example of the acyclic tertiary amine monomer is 3-(dimethylamino)propyl methacrylate, which may be present in the polymerizable composition in an amount of 0.5 wt.% to 3 wt.% or 1 wt.% to 2.5 wt.% (based on the total weight of the polymerizable composition). It has been found that compositions containing 3-(dimethylamino)propyl methacrylate provide contact lenses with particularly good dimensional stability.

[0047] As determined by the shelf life test method (wherein the chord diameter of twenty lenses from a single batch is measured and an average "original" diameter is obtained), if the contact lenses described herein are from a batch (i.e., lot) of contact lenses exhibiting an average dimensional stability with a variance of ≤ ±3.0% (i.e., less than or equal to plus or minus three percent), then the contact lenses are considered "dimensionally stable". At the same time, twenty unopened lens packages from the same batch are placed in an incubator set at 55 °C. The lenses are stored under these high temperature storage conditions for three months, which roughly corresponds to a two-year shelf life at 25 °C. At the end of three months, the encapsulated lenses are brought to room temperature, removed from their packages, and measured to obtain an average "final" diameter. By the equation: (diameter 最终 - diameter 原始 / diameter 原始) × 100 is used to calculate the dimensional stability variance. In some examples, the dimensional stability variance is ≤ ±2.5% or ≤ ±2.0% or ≤ ±1.5% or ≤ ±1.0%.

[0048] Generally, non-cyclic tertiary amine monomers (and a part of the polymer lens body) will form charged sites in a solution with a lower pH and / or a lower ionic strength, such as a pH below 8.0 or below 7 or under acidic conditions, such as a pH of 6 or lower (for example, a pH of 4 to 6). Under these conditions, the non-cyclic tertiary amine groups are protonated, thereby forming positively charged sites in the ophthalmic material. As further explained, these positively charged sites can form ionic complexes with negatively charged comfort agents or other releasable anionic agents.

[0049] Advantageously, one or more non-cyclic tertiary amine monomers are included in the polymerizable composition to provide a polymer lens body with a cation content of about 1.0% or 2.0% or 3.0% up to about 5.0%, 7.0%, or 10.0%. As used, "cation content" is a value determined by Formula I:

[0050] ∑(a n1 × b n1 / c n1 ) × 157 = cation content % (I)

[0051] Where a n1 is the weight percentage of the cationic monomer n1 used in the monomer mixture (as defined below), b n1 is the number of tertiary amine groups on the monomer n1, and c n1 is the molecular weight of the tertiary amine-containing monomer n1. If more than one tertiary amine-containing monomer is used in the polymerizable composition, then the tertiary amine content % of the resulting polymer lens body is the sum of the ionic content % provided by each tertiary amine-containing monomer (i.e., n1, n2, etc.). The weight percentage of the tertiary amine-containing monomer n1 in the polymerizable composition is relative to the weights of all components of the monomer mixture incorporated into the hydrogel. In other words, the components of the monomer mixture that are not incorporated into the final hydrogel product, such as diluents removed from the hydrogel during the manufacturing process, are not included in the weight percentage determination. Formula I adjusts for differences in molecular weight and charge with respect to 2-(dimethylamino)ethyl methacrylate (a exemplary tertiary amine-containing monomer with a molecular weight of 157 and one tertiary amine group).

[0052] As an option, one or more hydrophobic monomers can be present as part of the polymerizable composition.

[0053] Examples of suitable hydrophobic monomers include, but are not limited to, one or more silicon-free hydrophobic monomers. Examples of suitable hydrophobic monomers include: methyl acrylate, or ethyl acrylate, or propyl acrylate, or isopropyl acrylate, or cyclohexyl acrylate, or 2-ethylhexyl acrylate, or methyl methacrylate (MMA), or ethyl methacrylate, or propyl methacrylate, or butyl acrylate, or 2-hydroxybutyl methacrylate, or vinyl acetate, or vinyl propionate, or vinyl butyrate, or vinyl valerate, styrene, or chloroprene, or vinyl chloride, or vinylidene fluoride, or acrylonitrile, or 1-butene, or butadiene, or methacrylonitrile, or vinyltoluene, or vinyl ethyl ether, or perfluorohexylethylthiocarbonylaminoethyl methacrylate, or isobornyl methacrylate (IBM), or trifluoroethyl methacrylate, or hexafluoroisopropyl methacrylate, or tetrafluoropropyl methacrylate, or hexafluorobutyl methacrylate, or any combination thereof.

[0054] Based on the total weight of the polymerizable composition, the hydrophobic monomer (if used) can be present in the reaction product of the polymerizable composition in an amount of 1 wt.% to about 30 wt.%, such as 1 wt.% to 25 wt.%, 1 wt.% to 20 wt.%, 1 wt.% to 15 wt.%, 2 wt.% to 20 wt.%, 3 wt.% to 20 wt.%, 5 wt.% to 20 wt.%, 5 wt.% to 15 wt.%, 1 wt.% to 10 wt.%.

[0055] Additionally, or as an alternative to hydrophilic monomers, the polymerizable composition can contain a non-polymerizable hydrophilic polymer that results in a polymeric lens body comprising an interpenetrating polymer network (IPN) in which the non-polymerizable hydrophilic polymer interpenetrates the silicone hydrogel polymer matrix. In this example, the non-polymerizable hydrophilic polymer is referred to as an IPN polymer, which acts as an internal wetting agent in the contact lens. In contrast, the polymer chains within the silicone hydrogel network formed by polymerizing the monomers present in the polymerizable composition are not considered IPN polymers. The IPN polymer can be a high molecular weight hydrophilic polymer, such as from about 50,000 to about 500,000 daltons. In a specific example, the IPN polymer is polyvinylpyrrolidone (PVP). In other examples, the polymerizable composition does not contain or substantially does not contain polyvinylpyrrolidone or other IPN polymers.

[0056] The polymerizable composition may additionally comprise at least one crosslinking agent. As used herein, a "crosslinking agent" is a molecule having at least two polymerizable groups. Thus, the crosslinking agent can react with functional groups on two or more polymer chains to bridge one polymer to another. A variety of crosslinking agents suitable for silicone hydrogel polymerizable compositions are known in the art (see, for example, U.S. Patent No. 8,231,218, which is incorporated herein by reference). Examples of suitable crosslinking agents include, but are not limited to: lower alkylene glycol di(meth)acrylates, such as triethylene glycol dimethacrylate and diethylene glycol dimethacrylate; poly(lower alkylene) glycol di(meth)acrylates; lower alkylene di(meth)acrylates; allyl methacrylate; divinyl ethers, such as triethylene glycol divinyl ether, diethylene glycol divinyl ether, 1,4-butanediol divinyl ether, and 1,4-cyclohexanedimethanol divinyl ether; divinyl sulfone; divinylbenzene and trivinylbenzene; trimethylolpropane tri(meth)acrylate; pentaerythritol tetra(meth)acrylate; bisphenol A di(meth)acrylate; methylenebis(meth)acrylamide; triallyl phthalate; 1,3-bis(3-methacryloxypropyl)tetramethyldisiloxane; diallyl phthalate; triallyl isocyanurate, and combinations thereof.

[0057] As will be appreciated by those skilled in the art, the polymerizable composition may contain one or more additional polymerizable or non-polymerizable components conventionally used in contact lens formulations, such as a polymerization initiator, an oxygen scavenger, a chain transfer agent, a diluent, etc. In some instances, the polymerizable composition may include an amount of an organic diluent that can prevent or minimize phase separation between the hydrophilic and hydrophobic components of the polymerizable composition, thereby obtaining an optically clear lens. Diluents commonly used in contact lens formulations include hexanol, ethanol, and / or other primary, secondary, or tertiary alcohols. In other instances, the polymerizable composition does not contain or is substantially free of (e.g., less than 500 ppm) organic diluent. In these instances, the use of silicone monomers having a hydrophilic moiety containing, for example, polyethylene oxide groups, pendant hydroxyl groups, or other hydrophilic groups may obviate the need to include a diluent in the polymerizable composition. Non-limiting examples of these and additional components that may be included in the polymerizable composition are provided in U.S. Patent No. 8,231,218.

[0058] Specific examples of the silicone hydrogel contact lenses of the present invention are silicone hydrogel contact lenses based on a polymerizable composition, the polymerizable composition comprising: 25 wt.% to 55 wt.% of a siloxane monomer; 30 wt.% to 55 wt.% of a vinyl monomer selected from NVP, VMA or a combination thereof; and optionally about 1 wt.% to about 20 wt.% of a hydrophilic monomer selected from: N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA) or ethylene glycol methyl ether methacrylate (EGMA) or any combination thereof; and optionally about 1 wt.% to about 20 wt.% of a hydrophobic monomer selected from: methyl methacrylate (MMA), isobornyl methacrylate (IBM) or 2-hydroxybutyl methacrylate (HOB) or any combination thereof. The silicone hydrogel materials prepared from this specific embodiment of the polymerizable composition include Stanfilcon A, Confofilcon A, Somofilcon A, Vanfilcon A and Enfilcon A. In another example, the above polymerizable composition comprises the siloxane of Stanfilcon A, specifically a first siloxane having a structure represented by formula (I),

[0059]

[0060] and a second siloxane having a structure represented by formula (II),

[0061]

[0062] The above base polymerizable composition is further modified to additionally comprise 0.1 wt.% to 15 wt.% of at least one non-cyclic tertiary amine, such as (for example) 1 wt.% to 10 wt.% of 2-(dimethylamino)ethyl methacrylate or 0.5 wt.% to 3 wt.% of 3-(dimethylamino)propyl methacrylate, and is cured to provide a cationic polymer lens body.

[0063] As part of the present invention, the contact lens is a silicone hydrogel contact lens comprising a polymer lens body and at least one releasable anionic agent adhered to the polymer lens body. The anionic agent can adhere to the polymer lens body through cationic and / or hydrophobic interactions, and / or can be physically encapsulated through the polymer network of the polymer lens body. The releasable anionic agent can be one or more (for example, one, two or more) releasable anionic agents.

[0064] As an option, the releasable anionic agent can block TRPV1 receptors and / or can interact with PPARa receptors on the cornea.

[0065] Examples of releasable anionic agents include, but are not limited to, at least one acid. In a specific example, the anionic agent comprises a single carboxyl group. In another example, the anionic agent comprises two or more carboxyl groups. In one example, the anionic agent is a small molecule (i.e., having a molecular weight of less than about 900 daltons). In some examples, the releasable anionic agent is not a polymer as an option. As an option, the releasable anionic agent is not a polymer of disaccharides.

[0066] Examples of releasable anionic agents include, but are not limited to, at least one fatty acid. A more specific example of the releasable anionic agent is oleic acid.

[0067] When the releasable anionic agent is complexed via ionic interaction with the polymer lens body (e.g., due to low pH conditions and / or low ionic strength conditions, such as below about pH 7 or below about pH 6), in this state, the releasable anionic agent itself is an anionic agent or material complexed via ionic interaction with a cationic moiety or molecule that forms part of the polymer lens material. As an example, once deprotonated, the releasable anionic agent can form a complex with at least some protonated moieties or molecules in the polymer lens body, such as protonated tertiary amine groups present in the polymer lens body. The releasable anionic agent complexed via ionic interaction with the polymer lens body is released from the polymer lens body, such as by dissociation via ionic interaction with the relative ions in tears under physiological conditions. The anionic agent released at this time usually becomes a salt or an ester (e.g., a salt of at least one acid (such as oleic acid), or an oleic acid ester).

[0068] The amount of the releasable anionic agent adhered to the polymer lens body can be at least 25 μg, such as an amount from about 25 μg to 1000 μg or more, or from 25 μg to 700 μg, or from 25 μg to 650 μg, or from 25 μg to 600 μg, or from 25 μg to 550 μg, or from 25 μg to 500 μg, or from 25 μg to 450 μg, or from 25 μg to 400 μg, or from 25 μg to 350 μg, or from 25 μg to 300 μg, or from 25 μg to 250 μg, or from 50 μg to 750 μg, or from 75 μg to 750 μg, or from 100 μg to 750 μg, or from 125 μg to 700 μg, or from 150 μg to 700 μg, or from 175 μg to 700 μg, or from 200 μg to 700 μg, etc. In one example, the releasable anionic agent is oleic acid, which is adhered to the polymer lens body in an amount from about 25 μg to about 500 μg or from about 100 μg to about 300 μg. As used herein, the phrase "the amount of the releasable anionic agent adhered to the polymer lens body" refers to the total amount of the releasable anionic agent that can be extracted from the contact lens by a suitable extraction method, such as the isopropanol (IPA) extraction method described in Example 1 below.

[0069] As an option, the releasable anionic agent can be uniformly distributed throughout the polymer lens body by means of the ionic interactions described herein. As an option, the releasable anionic agent can be non-uniformly distributed. For example, the releasable anionic agent can be present in a higher amount on one side of the contact lens or on both sides (i.e., the posterior side and the anterior side) of the contact lens compared to the inner portion of the contact lens (the region between the posterior side and the anterior side).

[0070] The releasable anionic agent present in the silicone hydrogel contact lens is not covalently attached to the polymer lens body.

[0071] As an alternative or supplement to the ionic interactions described herein between the polymer lens body and the releasable anionic agent, the releasable anionic agent can, as an option, be considered to be embedded, trapped, dispersed, absorbed, and / or located within the contact lens. As mentioned, since the releasable anionic agent forms a complex with the contact lens material or a portion of the contact lens material (which would be considered an ionic interaction), the releasable anionic agent is preferably present within and / or on the surface of the contact lens.

[0072] Another example of the contact lens of the present invention is an unworn sterile silicone hydrogel contact lens comprising a polymer lens body that is a reaction product of a polymerizable composition comprising 15 wt.% to 65 wt.% of at least one siloxane monomer, 25 wt.% to 75 wt.% of at least one nonionic hydrophilic monomer, and 0.1 wt.% to 15 wt.% of at least one non-cyclic tertiary amine monomer. The unworn sterile silicone hydrogel contact lens is capable of releasing the releasable anionic agent at a release rate of at least 6 μg / hour for at least 8 hours. The amount or duration of release of the anionic agent from the contact lens as mentioned herein is intended to mean the amount and / or duration released from the contact lens when tested in the in vitro release assay described in Example 2. At least one non-cyclic tertiary amine monomer promotes the uptake and / or sustained release of the releasable anionic agent by the polymer lens body.

[0073] Regarding the promotion of uptake and / or sustained release of at least one releasable anionic agent by at least one acyclic tertiary amine monomer, this means that if a 'control lens' is compared with a 'cationic lens', the 'control lens' is a silicone hydrogel contact lens comprising a polymeric lens formed from a polymerizable composition that does not contain an acyclic tertiary amine monomer (but is otherwise the same polymerizable composition, except that a certain amount of the acyclic tertiary amine monomer is replaced by a hydrophobic monomer such as MMA), and the 'cationic lens' is a silicone hydrogel contact lens comprising a polymeric lens formed from a polymerizable composition having an acyclic tertiary amine monomer present, then the uptake of the polymeric lens containing the acyclic tertiary amine monomer will be higher than that of the control lens using the same concentration of the releasable anionic agent in the loading solution. Similarly, regarding the promotion of sustained release, the polymeric lens containing the acyclic tertiary amine monomer in the polymerizable composition will have a longer release period, such as 8 hours or 9 hours, compared to the control lens, and / or it will have a more linear release curve compared to the control lens over an 8-hour or 9-hour period. As used herein, the term "release curve" refers to the shape of the line when the amount of anionic agent released from the lens using the release medium and release analysis method described in Example 2 below is plotted at the 1-hour, 3-hour, 6-hour, and 9-hour time points, as Figure 1A shown in

[0074] In one example, the cationic contact lens exhibits a substantially linear release of the anionic agent for at least 8 hours. As used herein, if the linear regression of the anionic agent release curve has an R-squared value of at least 0.90 and the release amount is measured at the 1-hour, 3-hour, 6-hour, and 9-hour time points (n = 3 at each time point), then a substantially linear release for at least 8 hours is exhibited. In one example, the cationic contact lens exhibits a substantially linear release of the anionic agent for at least 8 hours and has an R-squared value of at least 0.90. In some examples, the cationic contact lens exhibits a substantially linear release of the anionic agent for at least 8 hours and has an R-squared value of at least 0.90, and the control lens exhibits a burst release, where 50 wt.% or more of the anionic agent releasable from the control lens is released within a period of 3 hours or less.

[0075] In some examples, the cationic contact lenses of the present invention can have an anionic agent release of 2 μg to 50 μg (such as 5 μg to 50 μg, or 10 μg to 40 μg or 10 μg to 30 μg) of anionic agent per hour for a period of at least 8 hours, at least 9 hours, or at least 10 hours, such as a period of 8 hours to 16 hours, or 10 hours to 16 hours, or 12 hours to 16 hours.

[0076] In the context of the present invention, it is preferably avoided that there is a burst release of the anionic agent. An example of burst release (or burst effect) is that 50 wt.% or more of the anionic agent releasable from the contact lens is released within a period of 3 hours or less.

[0077] Thus, in the context of the present invention, the contact lens of the present invention is capable of providing at least one or more of the following characteristics: a) a substantially linear release curve of the anionic agent, b) the ability to load a large amount of anionic agent (at least 50 μg, or at least 100 μg, or at least 150 μg or at least 200 μm into the lens), c) the anionic agent is released over a long period of time (at least 8 hours, such as 8 hours to 16 hours, or 9 hours to 16 hours, or 10 hours to 16 hours or 8 hours to 12 hours), and / or d) avoiding any burst release.

[0078] The uptake or loading of the releaseable anionic agent by the silicone hydrogel contact lens can occur during the extraction step and / or during the hydration step and / or during the encapsulation step. For example, the uptake of the releaseable anionic agent can occur during the solvent extraction step after the contact lens material has been cured and / or during one or more hydration steps, where at least one releaseable anionic agent is present in the extraction solvent and / or the hydration solution. Generally, if the anionic agent is not water-soluble, it is added to an organic extraction solvent such as ethanol or a mixture of ethanol and water. After curing, the polymer lens body swells in the extraction solvent containing the anionic agent. When the extracted polymer lens body is placed in a hydration solution such as deionized water, the extraction solvent is removed and the anionic agent remains in the hydrated polymer lens body. Generally, if the anionic agent is hydrophilic, it is included in the hydration solution or the final encapsulation solution, and the polymer lens body takes up the anionic agent from the hydration solution or the final encapsulation solution.

[0079] For example, the extraction and hydration liquids used in the extraction and hydration processes can consist of denatured ethanol, a 50 / 50 (by vol) mixture of denatured ethanol and deionized water, and deionized water. As an example, the extraction and hydration process can involve at least one extraction step in denatured ethanol, followed by an extraction step in a 50:50 mixture of ethanol and water, followed by at least one hydration step in deionized water, and each extraction and hydration step can be carried out at a temperature of about 20 °C to about 30 °C for about 15 minutes to about 3 hours. For the purposes of the present invention, any one or more or all of the liquids used for extraction and / or hydration can further contain one or more releaseable anionic agents to load the releaseable anionic agent into the polymer lens body. To achieve loading more effectively, the liquid can be adjusted to a pH of 7 or lower (such as about 4 to about 6).

[0080] In one example, the cationic silicone hydrogel contact lens contains at least 25% (by wt) (such as at least 50% or at least 75%) more releaseable anionic agent compared to a control lens.

[0081] As further described below, the unworn contact lens is typically placed in a base member containing a encapsulation solution after the extraction and hydration steps, and then the base member with the contact lens and the encapsulation solution is sealed and subjected to a sterilization process (such as autoclaving). As an option, the encapsulation solution may contain an amount of releaseable anionic agent such that this reagent is loaded into the contact lens after encapsulation. Preferably, the sterilization step does not affect the loading of the reagent in the contact lens or the encapsulation solution and also does not affect its stability.

[0082] As an option, the eye drop and / or the multi-purpose contact lens care solution (MPS) may contain a releaseable anionic agent. This option is particularly effective for reloading the contact lens with another releaseable anionic agent. Thus, another aspect of the present invention is the ability to reload the contact lens with a loading solution containing a releaseable anionic agent.

[0083] Any liquid used as a loading solution for the releaseable anionic agent may contain a releaseable anionic agent concentration of at least 50 ppm releaseable anionic agent. This concentration may be at least 100 ppm, at least 250 ppm, at least 500 ppm, at least 750 ppm, at least 1000 ppm, at least 1250 ppm, at least 1500 ppm, at least 1750 ppm or at least 2000 ppm of anionic agent. For example, the concentration of the anionic agent in the loading solution (or the solution used to load the anionic agent into the contact lens) may be 50 ppm to 2000 ppm or higher.

[0084] In some instances, the releasable anionic agent is stable after adhering to the polymeric lens body and substantially does not release or degrade from the polymeric lens body during autoclaving of a sealed contact lens package containing an unworn silicone hydrogel contact lens in a packaging solution or during storage in its packaging solution, but releases during lens wear. Thus, prior to autoclaving, or immediately after autoclaving, or 1 day after, or 30 days after, or 60 days after, or 120 days after, the packaging solution in which the contact lens is immersed has a releasable anionic agent released from the contact lens into the packaging solution of less than 10 ppm or less than 5 ppm or less than 1 ppm or 0 ppm. Whether the releasable anionic agent is released from the contact lens during autoclaving or storage can be determined by testing for the presence of the releasable anionic agent in the packaging solution using HPLC, LCMS, or other suitable analytical methods.

[0085] In the context of the present invention, one of the achievable features is to improve the comfort level of a soft contact lens, which includes reducing corneal sensitivity by releasing a reagent that blocks the TRPV1 receptor or interacts with the PPARa receptor on the cornea.

[0086] Furthermore, the present invention relates to a method of manufacturing a sealed contact lens package of the present invention or an unworn sterile silicone hydrogel contact lens comprising a polymeric lens body. The method comprises the steps of: a) polymerizing a polymerizable composition (as described herein) in a contact lens mold to obtain a hydrogel contact lens, b) removing the hydrogel contact lens from the contact lens mold, c) extracting and hydrating the removed hydrogel contact lens one or more times, d) sealing the hydrated silicone hydrogel contact lens in a package with a packaging solution, and e) autoclaving the package.

[0087] A silicone hydrogel material molded into a contact lens shape can generally be formed by curing a polymerizable composition (i.e., a monomer mixture) comprising at least one siloxane monomer, at least one hydrophilic monomer, and at least one tertiary amine monomer and optionally at least one hydrophobic monomer.

[0088] The contact lenses of the present invention can be manufactured using conventional methods. As an example, a polymerizable silicone hydrogel composition is dispensed into a female mold member having a concave surface that defines the front surface of the contact lens. A male mold member having a convex surface that defines the rear surface (i.e., the corneal contact surface) of the contact lens is combined with the female mold member to form a contact lens mold assembly, and the contact lens mold assembly is subjected to curing conditions (such as UV or heat curing conditions), under which the curable composition is formed into a polymeric lens body. The female mold member and the male mold member can be non-polar molds or polar molds. The mold assembly is disassembled (i.e., demolded), and the polymeric lens body is removed from the mold and the polymeric lens body is contacted with a solvent (such as an organic solvent, such as ethanol) to extract unreacted components from the lens body. After extraction, the lens body is hydrated in a hydrating liquid such as water or an aqueous solution. As indicated, a releasable anionic agent can be included in one or more extraction solvents for the extraction step, one or more hydrating liquids for the hydration step, or both the extraction solvent and the hydrating liquid.

[0089] If the releasable anionic agent is included in the extraction solvent, then the hydration step will displace the solvent with a hydrating liquid, thereby hydrating the polymeric lens body to form a silicone hydrogel, and the releasable anionic agent (or a portion thereof) can be retained via ionic interactions within the resulting silicone hydrogel. An exemplary method for manufacturing silicone hydrogel contact lenses is described in U.S. Patent No. 8,865,789.

[0090] The contact lenses in the present invention can be regarded as soft contact lenses, and in particular, soft silicone hydrogel contact lenses. The contact lenses sealed in the contact lens package of the present disclosure can have any wearing modality. The wearing modality of contact lenses refers to the number of consecutive days and nights that the contact lenses can be worn continuously without removal. In one example, the contact lenses sealed in the contact lens package of the present disclosure are daily disposable contact lenses. The daily disposable contact lenses are indicated for single use with continuous wear for up to about 12 or 16 hours, and should be discarded after single use. In another example, the contact lenses sealed in the contact lens package of the present disclosure are daily wear contact lenses. The daily wear contact lenses are worn during the waking hours, usually up to about 12 to 16 hours, and are removed before going to sleep. The daily wear contact lenses are usually stored in a contact lens case containing a contact lens care solution for cleaning and disinfecting the contact lenses during non-use periods. The daily wear contact lenses are usually discarded after being worn for at most 30 days. In yet another example, the contact lenses are extended wear contact lenses. The extended wear contact lenses are usually worn continuously for up to 6, 14, or 30 consecutive days and nights.

[0091] The encapsulation solution sealed within the contact lens package of the present disclosure can be any conventional contact lens compatible solution. In one example, the encapsulation solution comprises an aqueous solution of a buffering agent and / or a tonicity agent, consists of or consists essentially of an aqueous solution of a buffering agent and / or a tonicity agent. In another example, the encapsulation solution contains additional reagents, such as one or more additional antimicrobial agents and / or comfort agents and / or hydrophilic polymers, and / or a surfactant and / or other additives to prevent the lens from adhering to the surface of the package. The encapsulation solution can have a pH in the range of about 6.8 or 7.0 up to about 7.8 or 8.0. In one example, the encapsulation solution comprises a phosphate buffer or a borate buffer. In another example, the encapsulation solution comprises a tonicity agent selected from sodium chloride or sorbitol, in an amount that can maintain the osmolarity at about 200 to 400 mOsm / kg, and typically in the range of about 270 mOsm / kg up to about 310 mOsm / kg. In some examples, the encapsulation solution can comprise a polysaccharide (e.g., hyaluronic acid, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, etc.) or other high molecular weight polymers, such as polyvinylpyrrolidone, which are commonly used as comfort polymers or thickening agents in ophthalmic solutions and contact lens encapsulation solutions.

[0092] Regarding the contact lens package, the package can include or comprise a base member, such as a plastic base member, the base member comprising a cavity configured to retain the contact lens and the encapsulation solution and a flange region extending outwardly around the cavity. A removable foil or seal is attached to the flange region to provide a sealed contact lens package. Such contact lens packages, commonly referred to as "blister packs", are well known in the art (see, for example, U.S. Patent No. 7,426,993).

[0093] It should be understood that conventional manufacturing methods can be used to manufacture sealed contact lens packages. Thus, in one aspect of the present disclosure, a method of manufacturing a contact lens package includes the steps of placing an unworn contact lens and a contact lens encapsulation solution in a container, placing a lid on the container, and sealing the lid on the container. Generally, the container is configured to receive a single contact lens and an amount (usually about 0.5 to 1.5 ml) of encapsulation solution sufficient to completely cover the contact lens. The container can be made of any suitable material, such as glass or plastic. In one example, the container includes: a plastic base member that includes a cavity configured to retain the contact lens and the encapsulation solution and a flange region that extends outwardly around the cavity; and a lid that includes a removable foil attached to the flange region to provide a sealed contact lens package. The removable foil can be sealed by any conventional means, such as heat sealing or gluing. In another example, the container is in the form of a plastic base member that includes a plurality of threads, and the lid includes a plastic cap member that includes a set of compatible threads for engaging the threads of the base member, thereby providing a resealable lid. It should be understood that other types of encapsulations can also be used to provide a resealable package. For example, a contact lens package can include a plastic lid that includes components that engage compatible components of the container to form an interference fit.

[0094] The method of manufacturing a sealed contact lens package can further include sterilizing the unworn contact lens by subjecting the sealed contact lens package to autoclaving. Autoclaving generally involves subjecting the sealed contact lens package to a temperature of at least 121 °C for at least 20 minutes. The end product is a sterile, encapsulated silicone hydrogel contact lens with ocularly acceptable surface wettability. In a specific example, the present invention provides a contact lens package that includes: a base member having a cavity for receiving an encapsulation solution and a contact lens; an unworn silicone hydrogel contact lens in the cavity of the base member; and an encapsulation solution in the cavity of the base member.

[0095] The following examples illustrate certain aspects and advantages of the present invention, which should be understood as not being limited thereto.

[0096] Example 1. Uptake of oleic acid from cationic silicone hydrogel contact lenses

[0097] The following polymerizable compositions were used to prepare silicone hydrogel contact lenses: Stenfilcon A (control lenses) or Stenfilcon A modified to contain approximately 4.5 wt.% 2-(dimethylamino)ethyl methacrylate (cationic lenses). The polymerizable compositions were cured in polypropylene contact lens molds. The polymer lens bodies were removed from the molds and extracted by immersing them in ethanol (EtOH) containing oleic acid (Sigma) at the concentrations shown in Table I for 215 minutes. The lenses were removed from the EtOH and washed in a 50 / 50 EtOH / water mixture for approximately 30 minutes, followed by three changes of DI water, at approximately 6 minutes, 30 minutes, and 30 minutes of washing, respectively.

[0098] The amount of oleic acid (OA) in each lens (n = 3) was determined by extracting the lenses with isopropyl alcohol (IPA) and measuring the oleic acid in the extract by liquid chromatography - mass spectrometry (LCMS). Briefly, each lens was removed from its container, gently blotted to remove excess encapsulation solution, and each lens was placed in a 20 mL glass vial containing 10 mL of 100% isopropyl alcohol (IPA). The vials were placed on a tabletop shaker at 300 rpm at room temperature overnight (approximately 16 hours). For Stenfilcon A, a single overnight extraction step was sufficient to extract substantially all of the oleic acid from the lenses. More hydrophobic silicone hydrogel lens materials may require a second overnight extraction to extract all of the oleic acid, in which case the IPA from the first extraction step was removed and replaced with 3 mL of fresh IPA and shaken overnight at 300 rpm at room temperature. The amount of oleic acid in the IPA extract from each lens was determined by liquid chromatography - mass spectrometry (LCMS). The oleic acid loading concentration and the average oleic acid uptake per lens are shown in Table 1.

[0099] Table 1.

[0100] Glasses OA Loading Concentration Average Amount of OA / Glasses Control 750 ppm 59 μg Test 750 ppm 106 μg Control 1500 ppm 124 μg Test 1500 ppm 218 μg

[0101] Example 2. Release of oleic acid from cationic silicone hydrogel lenses.

[0102] An artificial tear film (ATF) having the composition shown in Table 2 was used as the in vitro release medium.

[0103] Table 2.

[0104] Component Concentration (mg / L) Sodium Chloride 5259.8 Potassium Chloride 1192.8 Sodium Citrate 441.09 Glucose 36.032 Urea 72.072 Calcium Chloride 55.49 Sodium Carbonate 1271.88 Potassium Bicarbonate 300.33 Disodium Hydrogen Phosphate 3407.04 Bovine Serum Albumin (Fatty Acid-Free) 2000 Lysozyme from Chicken Egg White 1900 Mucin from Bovine Submaxillary Gland 150 DI Water 1L Hydrochloric Acid (10 Molar, 37%) pH 7.1 - 7.2

[0105] Remove each contact lens from its container and shake to remove excess encapsulation solution. Transfer each contact lens (n = 3) to a 6 mL glass vial and add 5 mL of ATS pre-warmed to 35 °C to each vial. Place the vials in an incubator at 35 °C and shake at 125 rpm. Replace the release medium with 4.5 mL of fresh ATS at 1, 3, and 7 hours. Determine the amount of oleic acid in the contact lenses at each time point using the IPA extraction method described in Example 1. The results are shown in Table 3 and plotted in Figure 1A and Figure 1B .

[0106] Table 3.

[0107]

[0108] The linear regression equation and R-squared value of the release curve are provided in Table 4.

[0109] Table 4.

[0110]

[0111] Example 3. Dimensionally Stable Cationic Silicone Hydrogel Contact Lenses

[0112] Prepare silicone hydrogel contact lenses using a polymerizable composition of Stepanfilcon A modified to contain about 1.0 wt.%, 1.5 wt.%, 2.0 wt.%, and 2.5 wt.% of 3-(dimethylamino)propyl methacrylate (DMAPMA). Prepare the contact lenses using the method described in Example 1, except that oleic acid is not included in the extraction solvent. Determine the dimensional stability of the contact lenses using the storage life test method described above (i.e., store at 55 °C for three months, with a rough estimate of a two-year storage life at 25 °C). The average chord diameter of the contact lenses changes by less than 1.0% from the original average chord diameter, indicating that the contact lenses made with the DMAPMA monomer have dimensional stability.

[0113] The present invention includes the following numbered aspects / embodiments / features in any order and / or in any combination:

[0114] 1. An unworn sterile silicone hydrogel contact lens immersed in an encapsulation solution and sealed in an encapsulation, the contact lens comprising:

[0115] a. A polymer lens body that is a reaction product of a polymerizable composition comprising 15 wt.% to 65 wt.% of at least one silicone monomer, 25 wt.% to 75 wt.% of at least one nonionic hydrophilic monomer, and 0.5 wt.% to 3 wt.% of 3-(dimethylamino)propyl methacrylate; and

[0116] b. At least one releasable anionic agent that adheres to the polymeric lens body,

[0117] wherein 3-(dimethylamino)propyl methacrylate advantageously facilitates the uptake and / or sustained release of the at least one releasable anionic agent by the polymeric lens body.

[0118] 2. A contact lens according to any preceding or following embodiment / feature / aspect, wherein the polymerizable composition comprises from 1.0 wt.% to 2.5 wt.% of 3-(dimethylamino)propyl methacrylate.

[0119] 3. A contact lens according to any preceding or following embodiment / feature / aspect, wherein the polymerizable composition comprises from 1.5 wt.% to 2.0 wt.% of 3-(dimethylamino)propyl methacrylate.

[0120] 4. A contact lens according to any preceding or following embodiment / feature / aspect, wherein the polymerizable composition comprises a first siloxane monomer represented by Formula I and a second siloxane monomer represented by Formula II.

[0121] 5. A contact lens according to any preceding or following embodiment / feature / aspect, which has dimensional stability.

[0122] 6. A contact lens according to any preceding or following embodiment / feature / aspect, wherein the at least one releasable anionic agent is a fatty acid.

[0123] 7. A contact lens according to any preceding or following embodiment / feature / aspect, wherein the at least one releasable anionic agent is a small molecule.

[0124] 8. A contact lens according to any preceding or following embodiment / feature / aspect, wherein when placed in an artificial tear film solution, the sustained release of the at least one releasable anionic agent by the polymeric lens body is substantially linear for at least 8 hours.

[0125] 9. A contact lens according to any preceding or following embodiment / feature / aspect, wherein when placed in an artificial tear film solution, the sustained release of the at least one releasable anionic agent by the polymeric lens body is substantially linear for at least 8 hours, and wherein the linear regression of the release curve has an R-squared value of at least 0.90.

[0126] 10. A contact lens according to any of the foregoing or following embodiments / features / aspects, wherein when placed in an artificial tear film solution, the sustained release of the at least one releasable anionic agent from the polymeric lens body is substantially linear for at least 8 hours, wherein the linear regression of the release curve has an R-squared value of at least 0.90, and wherein the release curve of a control lens exhibits a burst release, wherein 50 wt.% or more of the anionic agent releasable from the control lens is released within a period of 3 hours or less.

[0127] 11. A contact lens according to any of the foregoing or following embodiments / features / aspects, wherein when placed in an artificial tear film solution, the sustained release of the at least one releasable anionic agent from the polymeric lens body is substantially linear for at least 8 hours, wherein the linear regression of the release curve has an R-squared value of at least 0.90, wherein the release curve of a control lens exhibits a burst release, wherein 50 wt.% or more of the anionic agent releasable from the control lens is released within a period of 3 hours or less, and wherein the releasable anionic agent is oleic acid.

[0128] 12. A contact lens according to any of the foregoing or following embodiments / features / aspects, wherein the encapsulating solution contains an additional releasable anionic agent that is the same as or different from the at least one releasable anionic agent.

[0129] 13. A contact lens according to any of the foregoing or following embodiments / features / aspects, wherein from about 25 μg to about 1000 μg of the releasable anionic agent adheres to the polymeric lens body.

[0130] 14. A contact lens according to any of the foregoing or following embodiments / features / aspects, wherein from about 100 μg to about 300 μg of the releasable anionic agent adheres to the polymeric lens body, and wherein the releasable anionic agent is oleic acid.

[0131] 15. A contact lens according to any of the foregoing or following embodiments / features / aspects, wherein the encapsulation comprises:

[0132] c. A base member having a cavity for retaining the encapsulating solution; and

[0133] d. A lid that forms a liquid-tight seal with the base member.

[0134] 16. A silicone hydrogel contact lens, which comprises a polymer lens body, and the polymer lens body is a reaction product of a polymerizable composition, the polymerizable composition comprising: 25 wt.% to 55 wt.% of a silicone monomer; 30 wt.% to 55 wt.% of a vinyl monomer selected from N-vinylpyrrolidone, N-vinyl-N-methylacetamide or a combination thereof; 0.5 wt.% to 3 wt.% of 3-(dimethylamino)propyl methacrylate; and optionally about 1 wt.% to about 20 wt.% of a hydrophilic monomer selected from the following: N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA) or ethylene glycol methyl ether methacrylate (EGMA) or any combination thereof; and optionally about 1 wt.% to about 20 wt.% of a hydrophobic monomer selected from the following: methyl methacrylate (MMA), isobornyl methacrylate (IBM) or 2-hydroxybutyl methacrylate (HOB) or any combination thereof.

[0135] 17. A method for manufacturing a silicone hydrogel contact lens as in any of the foregoing or following embodiments / features / aspects, the method comprising a) polymerizing the polymerizable composition in a contact lens mold to obtain the polymer lens body, b) removing the polymer lens body from the contact lens mold, c) extracting the polymer lens body in an extraction solvent, d) hydrating the polymer lens body in a hydrating liquid to obtain the silicone hydrogel contact lens, e) sealing the silicone hydrogel contact lens with a sealing solution in a package, and f) subjecting the package to high-pressure steam sterilization, wherein at least one of the extraction solvent, the hydrating liquid or the sealing solution contains the at least one releasable anionic agent.

[0136] 18. The method as in any of the foregoing or following embodiments / features / aspects, wherein the extraction solvent comprises the at least one releasable anionic agent.

[0137] 19. An unworn sterile silicone hydrogel contact lens, which comprises a polymer lens body, and the polymer lens body is a reaction product of a polymerizable composition, the polymerizable composition comprising: 15 wt.% to 65 wt.% of at least one silicone monomer, 25 wt.% to 75 wt.% of at least one nonionic hydrophilic monomer and 0.5 wt.% to 3 wt.% of 3-(dimethylamino)propyl methacrylate, and when tested in an in vitro release assay, the unworn sterile silicone hydrogel contact lens is capable of releasing the releasable anionic agent at a release rate of at least 6 μg / hour substantially linearly for at least 8 hours, wherein the 3-(dimethylamino)propyl methacrylate advantageously promotes the uptake and / or sustained release of the releasable anionic agent by the polymer lens body.

[0138] The disclosure of this document refers to certain illustrated examples, which should be understood as presented by way of example and not as a limitation. Although exemplary examples are discussed, the intent of the foregoing detailed description should be construed to cover all modifications, alternatives, and equivalents of the examples that may fall within the spirit and scope of the invention as defined by additional disclosure.

[0139] Unless a particular combination of features is mutually exclusive or the context otherwise indicates, references in this document to "examples" or "specific examples" or "aspects" or "embodiments" or similar phrases are intended to introduce one or more of the following features: a cationic silicone hydrogel contact lens or its components; a sealed contact lens package or its components; or a method of manufacturing a cationic silicone hydrogel contact lens, as appropriate to the context, which may be combined with any combination of examples, aspects, embodiments (i.e., features) described previously or subsequently. Further, as used in this specification, unless the context clearly indicates otherwise, the singular forms "a / an" and "the" include plural referents (e.g., at least one or more). Thus, for example, reference to "a contact lens" includes a single lens as well as two or more identical or different lenses.

[0140] The entire contents of all references cited in this disclosure are incorporated herein by reference to the extent not inconsistent with this disclosure.

[0141] The invention may include any combination of the various features or embodiments described in the claims above and / or below, as set forth in the clauses and / or paragraphs. Any combination of the features disclosed herein is considered part of the invention and no limitation is intended with respect to the features that may be combined.

[0142] Other embodiments of the invention will be apparent to those skilled in the art upon consideration of this specification and the practice of the invention disclosed herein. It is intended that this specification and the examples be considered only as exemplary, with the true scope and spirit of the invention being indicated by the following claims and their equivalents.

Claims

1. An unworn sterile silicone hydrogel contact lens immersed in a packaging solution and sealed in a package, the contact lens comprising: (a) A polymeric lens body, which is a reaction product of a polymerizable composition comprising 15 wt.% to 65 wt.% of at least one siloxane monomer, 25 wt.% to 75 wt.% of at least one nonionic hydrophilic monomer, and 0.5 wt.% to 3 wt.% of 3-(dimethylamino)propyl methacrylate; and (b) At least one releasable anionic agent adhered to the polymeric lens body, wherein the 3-(dimethylamino)propyl methacrylate facilitates the uptake and / or sustained release of the at least one releasable anionic agent by the polymeric lens body, wherein the polymerizable composition comprises a first siloxane monomer represented by Formula I: and a second siloxane monomer represented by Formula II:

2. The contact lens according to claim 1, wherein the polymerizable composition comprises 1.0 wt.% to 2.5 wt.% of 3-(dimethylamino)propyl methacrylate.

3. The contact lens according to claim 1, which has dimensional stability.

4. The contact lens according to claim 1, wherein the at least one releasable anionic agent is a fatty acid.

5. The contact lens according to claim 1, wherein the at least one releasable anionic agent is a small molecule.

6. The contact lens according to claim 1, wherein when placed in an artificial tear film solution, the sustained release of the at least one releasable anionic agent by the polymeric lens body is linear and lasts for at least 8 hours.

7. The contact lens according to claim 1, wherein when placed in an artificial tear film solution, the sustained release of the at least one releasable anionic agent by the polymeric lens body is linear and lasts for at least 8 hours, and wherein the linear regression of the release curve has an R-squared value of at least 0.

90.

8. The contact lens according to claim 1, wherein when placed in an artificial tear film solution, the sustained release of the at least one releasable anionic agent by the polymeric lens body is linear and lasts for at least 8 hours, wherein the linear regression of the release curve has an R-squared value of at least 0.90, and wherein the release curve of the control contact lens exhibits a burst release, wherein 50 wt.% or more of the anionic agent releasable from the control contact lens is released within a period of 3 hours or less.

9. The contact lens according to claim 1, wherein when placed in an artificial tear film solution, the sustained release of the at least one releasable anionic agent by the polymeric lens body is linear and lasts for at least 8 hours, wherein the linear regression of the release curve has an R-squared value of at least 0.90, wherein the release curve of the control contact lens exhibits a burst release, wherein 50 wt.% or more of the anionic agent releasable from the control contact lens is released within a period of 3 hours or less, and wherein the releasable anionic agent is oleic acid.

10. The contact lens according to claim 1, wherein the encapsulation solution comprises an additional releasable anionic agent that is the same as or different from the at least one releasable anionic agent.

11. The contact lens according to claim 1, wherein 25 μg to 1000 μg of the releasable anionic agent adheres to the polymeric lens body.

12. The contact lens according to claim 1, wherein 100 μg to 300 μg of the releasable anionic agent adheres to the polymeric lens body, and wherein the releasable anionic agent is oleic acid.

13. The contact lens according to claim 1, wherein the encapsulation comprises: (a) a base member having a cavity for receiving the encapsulation solution; and (b) a cover that forms a liquid-tight seal with the base member.

14. A silicone hydrogel contact lens comprising a polymeric lens body that is a reaction product of a polymerizable composition comprising: 25 wt.% to 55 wt.% of a silicone monomer; 30 wt.% to 55 wt.% of a vinyl monomer selected from N-vinylpyrrolidone, N-vinyl-N-methylacetamide, or a combination thereof; 0.5 wt.% to 3 wt.% of 3-(dimethylamino)propyl methacrylate; and optionally 1 wt.% to 20 wt.% of a hydrophilic monomer selected from: N,N-dimethylacrylamide, 2-hydroxyethyl methacrylate, ethoxyethyl methacrylamide, or ethylene glycol methyl ether methacrylate, or any combination thereof; and optionally 1 wt.% to 20 wt.% of a hydrophobic monomer selected from: methyl methacrylate, isobornyl methacrylate, or 2-hydroxybutyl methacrylate, or any combination thereof, wherein the polymerizable composition comprises a first silicone monomer represented by Formula I: and a second silicone monomer represented by Formula II:

15. The contact lens according to claim 14, wherein the polymerizable composition comprises 1.0 wt.% to 2.5 wt.% of 3-(dimethylamino)propyl methacrylate.

16. The contact lens according to claim 14, which has dimensional stability.

17. A method of manufacturing the silicone hydrogel contact lens according to claim 1, the method comprising a) polymerizing the polymerizable composition in a contact lens mold to obtain the polymeric lens body, b) removing the polymeric lens body from the contact lens mold, c) extracting the polymeric lens body in an extraction solvent, d) hydrating the polymeric lens body in a hydrating liquid to obtain the silicone hydrogel contact lens, e) sealing the silicone hydrogel contact lens with an encapsulation solution in an encapsulation, and f) autoclaving the encapsulation, wherein at least one of the extraction solvent or the hydrating liquid or the encapsulation solution contains the at least one releasable anionic agent.

18. The method according to claim 17, wherein the extraction solvent comprises the at least one releasable anionic agent.

19. An unworn sterile silicone hydrogel contact lens, which comprises a polymeric lens body, and the polymeric lens body is a reaction product of a polymerizable composition, and the polymerizable composition comprises: at least one silicone monomer of 15 wt.% to 65 wt.%, at least one nonionic hydrophilic monomer of 25 wt.% to 75 wt.%, and 3-(dimethylamino)propyl methacrylate of 0.5 wt.% to 3 wt.%, and when tested in an in vitro release assay, the unworn sterile silicone hydrogel contact lens is capable of linearly releasing a releasable anionic agent at a release rate of at least 6 μg / hour for at least 8 hours, wherein the 3-(dimethylamino)propyl methacrylate facilitates the uptake and / or sustained release of the releasable anionic agent by the polymeric lens body, wherein the polymerizable composition comprises a first silicone monomer represented by Formula I: and a second silicone monomer represented by Formula II:

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